19-19186956-GGA-CGG

Variant names:

• chr19-19186956-GGA-CGG
• NM_001145784.2:c.85_87delTCCinsCCG
• BORCS8 p.Ser29Pro

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001145784.2(BORCS8):​c.85_87delTCCinsCCG​(p.Ser29Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BORCS8 NM_001145784.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.76
• Publications: 0 publications found

Genes affected

BORCS8 (HGNC:37247): (BLOC-1 related complex subunit 8) Involved in heart development. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS8-MEF2B (HGNC:39979): (BORCS8-MEF2B readthrough) This gene represents numerous read-through transcripts that span GeneID:729991 and 100271849. Many read-through transcripts are predicted to be nonsense-mediated decay (NMD) candidates, and are thought to be non-coding. Some transcripts are predicted to be capable of translation reinitiation at a downstream AUG, resulting in expression of at least one isoform of myocyte enhancer factor 2B (MEF2B) from this read-through locus. At least one additional MEF2B variant and isoform can be expressed from a downstream promoter, and is annotated on GeneID:100271849. [provided by RefSeq, Oct 2010]

MEF2B (HGNC:6995): (myocyte enhancer factor 2B) The product of this gene is a member of the MADS/MEF2 family of DNA binding proteins. The protein is thought to regulate gene expression, including expression of the smooth muscle myosin heavy chain gene. This region undergoes considerable alternative splicing, with transcripts supporting two non-overlapping loci (GeneID 729991 and 100271849) as well as numerous read-through transcripts that span both loci (annotated as GeneID 4207). Several isoforms of this protein are expressed from either this locus or from some of the read-through transcripts annotated on GeneID 4207. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145784.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS8	NM_001145784.2	MANE Select	c.85_87delTCCinsCCG	p.Ser29Pro	missense	N/A	NP_001139256.1	Q96FH0-1
	BORCS8	NM_001145783.2		c.85_87delTCCinsCCG	p.Ser29Pro	missense	N/A	NP_001139255.1	Q96FH0-2
	BORCS8-MEF2B	NM_005919.4		c.-216-4275_-216-4273delTCCinsCCG		intron	N/A	NP_005910.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS8	ENST00000462790.8	TSL:1 MANE Select	c.85_87delTCCinsCCG	p.Ser29Pro	missense	N/A	ENSP00000425864.1	Q96FH0-1
	BORCS8	ENST00000477565.3	TSL:1	c.85_87delTCCinsCCG	p.Ser29Pro	missense	N/A	ENSP00000424833.1	Q96FH0-2
	BORCS8-MEF2B	ENST00000514819.7	TSL:5	c.-89-4275_-89-4273delTCCinsCCG		intron	N/A	ENSP00000454967.3	H3BNR1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-19297765;